The overall goal of this research is to better understand the relationships of genetics, structure, and function of hemoglobins in both humans and other selected animals. This goal is divided into five specific objectives: 1) structural characterization of new abnormal human hemoglobins sent to our laboratory for further study; 2) determination of the structure of the zeta chain of the embryonic hemoblobin Portland 1; 3) characterization and determination of mechanisms of formation of the normal minor hemoglobin components AIa, AIb, and AIc; 4) determination and comparison of sequences of selected animal hemoglobins with each other and with known sequences of other animals; and 5) correlation of structure and function differences observed for human hemoglobin variants and other animal hemoglobins in order to obtain more understanding of the relationships of structure and function at the molecular level. This latter objective is partly dependent upon another research project of this laboratory which is directed at a detailed study of the oxygen binding equilibria of abnormal human hemoglobins. These objectives will be pursued by the chemical characterization of abnormal hemoblobins selected because they appear to be new and previously unreported mutants or because they are known mutants but found in informative family arrangements or populations. Unknown abnormal hemoglobins will be accepted from any source for further characterization; however, most new samples are expected to come from referral sources which already exist. All will be studied and reported in collaboration with the referring source. The zeta chain will be isolated from Hb Portland 1 obtained from blood from stillbirth infants with hydrops fetalis. Animal hemoglobins will be selected because of special genetic of evolutionary reasons or because of unusual chemical properties in comparison to human hemoglobins.